Several major aspects of senile dementia are being investigated in this project: The Alzheimer type (SDAT) accounts for about 50%, and the multi-infarct type (MID) for another 25% of the cases of this disorder, of which there are more than one million severe examples in this country. We are attempting to identify risk factors for these dementias in a prospective study involving 400 congnitively normal volunteers between the ages of 74 and 85. Cardiovascular risk factors for MID (including arrythmias, hypertension, etc.) are being intensively investigated. Special attention is given to serum lipids and lipoproteins, especially HDL and its subclasses as risk factors for stroke and dementia. Both possible exogenous and metabolic risk factors for Alzheimer's disease are being sought. The volunteers participate in the epidemiological, medical, neurological and psychological evaluations. Over a period of 6 years approximately one third of the subjects will develop dementing diseases affording an opportunity to follow the natural history of these disorders from their onset, and to study the development of intrusions and other neuropsychological phenomena. We will seek to identify criteria that might help in the differential diagnosis of dementia.